Risk assessment for newly diagnosed, fit and young patients with Multiple Myeloma, in the era of novel treatment modalities: Are there any additional factors to be under consideration?

Abstract

Multiple myeloma (MM) is considered a disease of elderlies however, 35-40% of newly diagnosed MM (NDMM) patients (pts) are ≤60 years (ys) old. Although young NDMM pts succeed better outcomes with the currently used treatment protocols, a considerable number of them (25-35%) succumb to MM, within 5 ys after diagnosis. We evaluated the overall survival (OS) and the related risk factors, in NDMM pts aged ≤55 years and we designed a scoring system with predictive value on their long-term outcome. Among 116 NDMM pts treated from 2010-20 in our center, 58 were ≤55 ys and 41% had advanced disease, 24% elevated LDH, 15% extramedullary disease (EMD) and 14% high-risk cytogenetic features. Following treatment with 3 (n=48) or 2 (n=10) agents of Velcade, Cyclophosphamide, Lenalidomide and DXM, 90% underwent autologous hematopoietic stem cell transplantation (AHSCT). Female gender, advance disease, EMD presence, elevated LDH and less than very good response pre-AHSCT, adversely affected the OS. After a median follow up of 4 ys, the median OS was not reached however, approximately 25% of young NDMM patients died within 4 ys after diagnosis. Based on the aforementioned risk factors we created a risk scoring system which compared to the international staging system (ISS), sufficiently discriminated young NDMM patients who are at risk for poor outcome. The 4-year OS was superior for pts with 0-2 factors compared to those with 3-5 factors (86% vs. 44% respectively, p<0.001). Despite the current plethora of the available treatment agents, the heterogeneity in the outcomes among the NDMM pts, highlights the unmet need to establish appropriate criteria for personalized and more efficient treatment approaches, especially for the younger NDMM pts. In this study, we propose an easily applicable scoring system, which can discriminate younger NDMM pts who might need more intensive treatment aiming at prolonged survival rates.